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Regulation of phototransduction responsiveness and retinal degeneration by a phospholipase D-generated signaling lipid.

LaLonde MM, Janssens H, Rosenbaum E, Choi SY, Gergen JP, Colley NJ, Stark WS, Frohman MA - J. Cell Biol. (2005)

Bottom Line: Drosophila melanogaster phototransduction proceeds via a phospholipase C (PLC)-triggered cascade of phosphatidylinositol (PI) lipid modifications, many steps of which remain undefined.We describe the involvement of the lipid phosphatidic acid and the enzyme that generates it, phospholipase D (Pld), in this process.Pld() flies exhibit decreased light sensitivity as well as a heightened susceptibility to retinal degeneration.

View Article: PubMed Central - PubMed

Affiliation: Program in Molecular and Cellular Biology, Center for Developmental Genetics, Stony Brook University, Stony Brook, NY 11794, USA.

ABSTRACT
Drosophila melanogaster phototransduction proceeds via a phospholipase C (PLC)-triggered cascade of phosphatidylinositol (PI) lipid modifications, many steps of which remain undefined. We describe the involvement of the lipid phosphatidic acid and the enzyme that generates it, phospholipase D (Pld), in this process. Pld() flies exhibit decreased light sensitivity as well as a heightened susceptibility to retinal degeneration. Pld overexpression rescues flies lacking PLC from light-induced, metarhodopsin-mediated degeneration and restores visual signaling in flies lacking the PI transfer protein, which is a key player in the replenishment of the PI 4,5-bisphosphate (PIP2) substrate used by PLC to transduce light stimuli into neurological signals. Altogether, these findings suggest that Pld facilitates phototransduction by maintaining adequate levels of PIP2 and by protecting the visual system from metarhodopsin-induced, low light degeneration.

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Endogenous levels of Pld action protect against retinal degeneration. Retinal tissue sections were prepared from flies raised under continuous light for 1 or 6 d: (A and C) norpA7 and (B and D) norpA7; Pld. Although the norpA7 (A) mutant flies had a fairly normal retinal morphology with intact photoreceptor cells and cell bodies soon after eclosion (and the Pld was indistinguishable from wild type; not depicted), the Pld; norpA7 double mutant (B) already displayed advanced degeneration, with small rhabdomeres and severely reduced cell bodies. No cell bodies were evident except for photoreceptor R7/8. By 6 d after eclosion, degeneration in the norpA7 (C) mutant was becoming evident (smaller rhabdomeres and some vacuolation); however, by this time, the norpA7; Plddouble mutant (D) had undergone extensive retinal degeneration, with only rhabdomeres R7/8 remaining apparent in some ommatidia.
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fig7: Endogenous levels of Pld action protect against retinal degeneration. Retinal tissue sections were prepared from flies raised under continuous light for 1 or 6 d: (A and C) norpA7 and (B and D) norpA7; Pld. Although the norpA7 (A) mutant flies had a fairly normal retinal morphology with intact photoreceptor cells and cell bodies soon after eclosion (and the Pld was indistinguishable from wild type; not depicted), the Pld; norpA7 double mutant (B) already displayed advanced degeneration, with small rhabdomeres and severely reduced cell bodies. No cell bodies were evident except for photoreceptor R7/8. By 6 d after eclosion, degeneration in the norpA7 (C) mutant was becoming evident (smaller rhabdomeres and some vacuolation); however, by this time, the norpA7; Plddouble mutant (D) had undergone extensive retinal degeneration, with only rhabdomeres R7/8 remaining apparent in some ommatidia.

Mentions: 1 d after eclosion, neither the Pld (not depicted, but see Fig. 3 D) nor the norpA7 (Fig. 7 A) mutants individually displayed retinal degeneration, and, in fact, retinal degeneration in norpA7 did not become evident until several days later (Fig. 7 C). However, at 1 d after eclosion, the Pld; norpA7double mutant (Fig. 7 B) already exhibited initial signs of degeneration with small rhabdomeres and decreased cell body size. By 6 d after eclosion, retinal degeneration in the Pld; norpA7double mutant was sufficiently advanced so that only R7/8 remained intact (Fig. 7 D). Together with the previous findings, these results demonstrate that Pld plays physiological roles both in supporting PIP2 levels during phototransduction and in maintaining photoreceptor viability in the absence of ongoing phototransduction events.


Regulation of phototransduction responsiveness and retinal degeneration by a phospholipase D-generated signaling lipid.

LaLonde MM, Janssens H, Rosenbaum E, Choi SY, Gergen JP, Colley NJ, Stark WS, Frohman MA - J. Cell Biol. (2005)

Endogenous levels of Pld action protect against retinal degeneration. Retinal tissue sections were prepared from flies raised under continuous light for 1 or 6 d: (A and C) norpA7 and (B and D) norpA7; Pld. Although the norpA7 (A) mutant flies had a fairly normal retinal morphology with intact photoreceptor cells and cell bodies soon after eclosion (and the Pld was indistinguishable from wild type; not depicted), the Pld; norpA7 double mutant (B) already displayed advanced degeneration, with small rhabdomeres and severely reduced cell bodies. No cell bodies were evident except for photoreceptor R7/8. By 6 d after eclosion, degeneration in the norpA7 (C) mutant was becoming evident (smaller rhabdomeres and some vacuolation); however, by this time, the norpA7; Plddouble mutant (D) had undergone extensive retinal degeneration, with only rhabdomeres R7/8 remaining apparent in some ommatidia.
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Related In: Results  -  Collection

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fig7: Endogenous levels of Pld action protect against retinal degeneration. Retinal tissue sections were prepared from flies raised under continuous light for 1 or 6 d: (A and C) norpA7 and (B and D) norpA7; Pld. Although the norpA7 (A) mutant flies had a fairly normal retinal morphology with intact photoreceptor cells and cell bodies soon after eclosion (and the Pld was indistinguishable from wild type; not depicted), the Pld; norpA7 double mutant (B) already displayed advanced degeneration, with small rhabdomeres and severely reduced cell bodies. No cell bodies were evident except for photoreceptor R7/8. By 6 d after eclosion, degeneration in the norpA7 (C) mutant was becoming evident (smaller rhabdomeres and some vacuolation); however, by this time, the norpA7; Plddouble mutant (D) had undergone extensive retinal degeneration, with only rhabdomeres R7/8 remaining apparent in some ommatidia.
Mentions: 1 d after eclosion, neither the Pld (not depicted, but see Fig. 3 D) nor the norpA7 (Fig. 7 A) mutants individually displayed retinal degeneration, and, in fact, retinal degeneration in norpA7 did not become evident until several days later (Fig. 7 C). However, at 1 d after eclosion, the Pld; norpA7double mutant (Fig. 7 B) already exhibited initial signs of degeneration with small rhabdomeres and decreased cell body size. By 6 d after eclosion, retinal degeneration in the Pld; norpA7double mutant was sufficiently advanced so that only R7/8 remained intact (Fig. 7 D). Together with the previous findings, these results demonstrate that Pld plays physiological roles both in supporting PIP2 levels during phototransduction and in maintaining photoreceptor viability in the absence of ongoing phototransduction events.

Bottom Line: Drosophila melanogaster phototransduction proceeds via a phospholipase C (PLC)-triggered cascade of phosphatidylinositol (PI) lipid modifications, many steps of which remain undefined.We describe the involvement of the lipid phosphatidic acid and the enzyme that generates it, phospholipase D (Pld), in this process.Pld() flies exhibit decreased light sensitivity as well as a heightened susceptibility to retinal degeneration.

View Article: PubMed Central - PubMed

Affiliation: Program in Molecular and Cellular Biology, Center for Developmental Genetics, Stony Brook University, Stony Brook, NY 11794, USA.

ABSTRACT
Drosophila melanogaster phototransduction proceeds via a phospholipase C (PLC)-triggered cascade of phosphatidylinositol (PI) lipid modifications, many steps of which remain undefined. We describe the involvement of the lipid phosphatidic acid and the enzyme that generates it, phospholipase D (Pld), in this process. Pld() flies exhibit decreased light sensitivity as well as a heightened susceptibility to retinal degeneration. Pld overexpression rescues flies lacking PLC from light-induced, metarhodopsin-mediated degeneration and restores visual signaling in flies lacking the PI transfer protein, which is a key player in the replenishment of the PI 4,5-bisphosphate (PIP2) substrate used by PLC to transduce light stimuli into neurological signals. Altogether, these findings suggest that Pld facilitates phototransduction by maintaining adequate levels of PIP2 and by protecting the visual system from metarhodopsin-induced, low light degeneration.

Show MeSH
Related in: MedlinePlus